title: Diversity of the human LILRB3/A6 locus encoding a myeloid inhibitory and activating receptor pair.
abstract: Leukocyte immunoglobulin-like receptor (LILR)B3 and LILRA6 represent a pair of inhibitory/activating receptors with identical extracellular domains and unknown ligands. LILRB3 can mediate inhibitory signaling via immunoreceptor tyrosine-based inhibition motifs in its cytoplasmic tail whereas LILRA6 can signal through association with an activating adaptor molecule, FcRγ, which bears a cytoplasmic tail with an immunoreceptor tyrosine-based activation motif. The receptors are encoded by two highly polymorphic neighboring genes within the leukocyte receptor complex on human chromosome 19. Here, we report that the two genes display similar levels of single nucleotide polymorphisms with the majority of polymorphic sites being identical. In addition, the LILRA6 gene exhibits copy number variation (CNV) whereas LILRB3 does not. A screen of healthy Caucasians indicated that 32 % of the subjects possessed more than two copies of LILRA6, whereas 4 % have only one copy of the gene per diploid genome. Analysis of mRNA expression in the major fractions of PBMCs showed that LILRA6 is primarily expressed in monocytes, similarly to LILRB3, and its expression level correlates with copy number of the gene. We suggest that the LILRA6 CNV may influence the level of the activating receptor on the cell surface, potentially affecting signaling upon LILRB3/A6 ligation.
authors.affiliation: Cancer and Inflammation Program, Laboratory of Experimental Immunology, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, USA.
authors.forename: Arman A
authors.initials: AA
authors.lastname: Bashirova
authors.forename: Richard
authors.initials: R
authors.lastname: Apps
authors.forename: Nicolas
authors.initials: N
authors.lastname: Vince
authors.forename: Yelizaveta
authors.initials: Y
authors.lastname: Mochalova
authors.forename: Xu G
authors.initials: XG
authors.lastname: Yu
authors.forename: Mary
authors.initials: M
authors.lastname: Carrington
mesh_terms: D015703:Antigens, CD / Q000235:genetics*; D002648:Child; D015331:Cohort Studies; D004247:DNA / Q000032:analysis / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics*; D005190:Family; D005260:Female; D006801:Humans; D008297:Male; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D011971:Receptors, Immunologic / Q000235:genetics*
chemical_list: D015703:Antigens, CD; C527699:LILRB3 protein, human; D012333:RNA, Messenger; D011971:Receptors, Immunologic; C413086:leukocyte-immunoglobulin--like receptor 6; D004247:DNA